OBJECTIVE: The overall objective of this proposal is to investigate the effect of sex hormones on aortic collagen and elastin metabolism in normal and atherosclerotic animals and to relate these hormonal effects on connective tissue to alterations in the development of atherosclerosis. Twelve different groups of rats will be studied, six groups of which will be administered an atherogenic diet. The following studies will be done on aortas of rats from all the groups: synthesis, degradation, and total accumulation of collagen and elastin; total glycosaminoglycan content; total cholesterol content; concentration of calcium; histologic sections. The studies are based on the hypothesis that certain sex hormones increase turnover of collagen and elastin in blood vessels and in so doing retard the development of pre-atheromatous biochemical changes and atheromatous plaque development. METHODS: Castrated female rats will be administered oil or estradiol; normal female rats will be administered oil or norethynodrel-mestranol combination; normal male rats will be administered oil or anti-androgen drug. Rats in six of the groups will be fed a normal diet, and they will be paired with rats of the other six groups which will be fed an atherogenic diet. After two months of diet regimen, some rats from each group will be administered 14C-proline. These rats will be killed at one day or one month after administration of the radioactivity and specific activity of hydroxyproline and proline in collagen and elastin or aortas will be determined. All other rats will be killed after three months on the diets and aortas will be examined grossly and histologically for atherosclerotic changes and for the biochemical changes mentioned above. In addition systolic blood pressure will be measured in every rat at monthly intervals and plasma cholesterol and triglycerides will be determined.